Characterisation Of Human Embryonic Stem Cell Differentiation To Haematopoietic Progenitors And Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$638,856.00
Summary
Blood stem cells, which are found in the bone marrow, are currently used for treating human blood disorders including leukemia and lymphoma. However, for the majority of bone marrow transplant candidates, suitable donors cannot be found. Using embryonic stem cells, this project aims to define the conditions required to generate blood stem cells in the laboratory. The aim of the work is to provide a new source of blood stem cells that could be used in place of donor derived bone marrow.
Mechanisms Guiding Pathfinding And Positioning Of Cortical Interneurons
Funder
National Health and Medical Research Council
Funding Amount
$621,606.00
Summary
Brain disorders place an economic and social burden on Australia and the personal costs of these illnesses are immeasurable. Several brain abnormalities are caused from the failure of neurons to position themselves in the correct location when the brain develops. Our study aims to discover how neurons move and what factors influence this process. It provides an understanding of normal brain development, as well as providing insight into what may go wrong in the formation of brain diseases.
Identification Of Novel Mechanisms Governing Stage-specific Regulation Of The Human Globin Genes
Funder
National Health and Medical Research Council
Funding Amount
$481,826.00
Summary
Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases worldwide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing embryo, fetal hemoglobin. We have identified key factors important for fetal gene expression. Our goal is to translate these findings into therapies for the hemoglobin disorders.
The Role Of Cell Adhesion Molecules In Regulation Of Axon Advance
Funder
National Health and Medical Research Council
Funding Amount
$426,006.00
Summary
All cells contain on their surface a class of molecules, cell adhesion molecules, that enable them to adhere to other cells in tissues. Cell adhesion molecules have long been known to be involved in the guidance of axons to their targets during development. However the molecular mechanisms by which these molecules act are largely unknown. We propose to use the powerful genetic tools available in the fruitfly to dissect the mechanisms by which two cell adhesion molecules promote axon growth.
Cellular Mechanisms Controlling Neural Crest Cell Migration Along The Developing Gut
Funder
National Health and Medical Research Council
Funding Amount
$368,895.00
Summary
Within the wall of the gut, there are a large number of neurons, probably more than are in the spinal cord. These enteric neurons play an essential role in controlling a number of gut functions including peristalsis (the propulsion of contents along the gut). Most of the neurons in the gut, including those in the large intestine, arise from precursors that emigrate from the hindbrain, and then migrate into and along the gastrointestinal tract during development. The colonization of the gut by ne ....Within the wall of the gut, there are a large number of neurons, probably more than are in the spinal cord. These enteric neurons play an essential role in controlling a number of gut functions including peristalsis (the propulsion of contents along the gut). Most of the neurons in the gut, including those in the large intestine, arise from precursors that emigrate from the hindbrain, and then migrate into and along the gastrointestinal tract during development. The colonization of the gut by neuron precursors takes 5 days in mice and 6 weeks in humans. Studies of the mechanisms controlling the migration of neuron precursors along the gut have provided fundamental information about cell migration in general. Genetic studies in humans and mice have identified some of the genes that are necessary for the migration of neuron precursors along the gastrointestinal tract, but for some of the key genes, their precise role is unknown. We have recently developed a method for imaging living neuron precursors migrating through explants of embryonic mouse gut. In the current proposal we will meld imaging and genetic studies to understand how mutations in particular genes lead to migration defects. In particular, how do particular mutations affect the migratory behaviour of enteric neural precursors? We have also previously shown that neuron precursors migrate along the gut in close association with axons. We will examine the nature of these interactions - in particular, who is following whom, and what happens when cell migration and axon growth are uncoupled? These studies, which will investigate a number of critical aspects of the migration of neural precursors into and along the developing gut, are central to understanding how the enteric nervous system is established along the gastrointestinal tract.Read moreRead less
Shared Team Approach Between Nurses And Doctors For Improved Risk Factor Management (STAND FIRM)
Funder
National Health and Medical Research Council
Funding Amount
$1,945,676.00
Summary
There are many proven treatments for preventing people with stroke from having a recurrent event, e.g. maintaining blood pressure at acceptable levels. However, uptake of therapies is poor. We will assess whether patients receiving individualised management plans, prepared and administered by both doctors and nurses will have risk factors controlled better than those receiving usual care. The plan includes education of patients to help them have more control over their own care.
A Study Of The Molecular Epidemiology And Virulence Determinants Of Enterovirus 71 Strains From The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$286,325.00
Summary
In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to ....In this study, we aim to understand the reasons for the emergence of epidemics of severe neurological disease due to enterovirus 71 (EV71) in young children of the Asia-Pacific region since 1997, and to develop strategies for disease prevention. EV71 is a human enterovirus closely related to the polioviruses. Most infections with EV71 are trivial, however, they may occasionally result in severe disease, including brainstem encephalitis with a high mortality and acute flaccid paralysis similar to poliomyelitis. There has been a large increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997, including a large epidemic in Perth, Western Australia in 1999. These epidemics have resulted in many deaths and cases of severe neurological disability. In view of the severity of EV71 neurological disease and the lack of effective treatments, our research effort needs to focus on prevention through public health surveillance and vaccine development. The major aims of our study are two-fold: 1. To study the origin and evolution of EV71 in the Asia-Pacific region using molecular techniques and to use this information to implement surveillance in Australia and Southeast Asia. It is anticipated that improved surveillance will provide early warning of impending epidemics. 2. To understand the molecular basis of virulence of EV71, with emphasis on the ability of virus to cause severe disease of the central nervous system. This study will have two goals: a. To identify the human cellular receptor of EV71. The ultimate goal of this research will be the development of a small animal model of EV71 encephalitis by constructing a transgenic mouse expressing the human cellular receptor for EV71. b. To construct an infectious cDNA clone of EV71 and to develop genetically defined attenuated strains by mutagenesis of the infectious clone. Mutant strains of EV71 will be tested for replication and virulence in newborn mice and in human neuroblastoma cells.Read moreRead less
Brain Protection: A new therapeutic approach for Multiple Sclerosis In Multiple Sclerosis (MS), the immune system mistakenly attacks the brain. The immune attacks destroy myelin, the protective coat around electrical cables in the brain (demyelination). Current treatments for MS are only partially effective, and work by reducing the number and severity of these attacks. However, MS-related permanent disability in the majority of sufferers is due to the development of progressive MS, and current ....Brain Protection: A new therapeutic approach for Multiple Sclerosis In Multiple Sclerosis (MS), the immune system mistakenly attacks the brain. The immune attacks destroy myelin, the protective coat around electrical cables in the brain (demyelination). Current treatments for MS are only partially effective, and work by reducing the number and severity of these attacks. However, MS-related permanent disability in the majority of sufferers is due to the development of progressive MS, and current therapies do not reduce this progression. It is believed that one major cause of this permanent disability is permanent myelin loss. Interestingly, we have already shown that the growth factor LIF is made by the body during MS-like inflammation, and that it limits damage by directly protecting myelin-producing cells. However, the bodies own LIF production during inflammation is sub-maximal, because myelin protection can be enhanced by giving additional therapeutic LIF. This suggests that (1) The brain produces a defence response to harmful inflammation and that (2) This defence response can be enhanced therapeutically. We therefore want to define exactly how LIF enhances myelin survival. We have measured the response to LIF in myelin-producing cells, and have discovered that it strongly stimulates the production of the small protein galanin. We will now assess if galanin itself protects myelin and myelin-producing cells, and we will test this both in isolated cells and whole animal models. If galanin production is a major mechanism by which the body tries to limit the damage from abnormal inflammation during MS, then medications that mimic the action of galanin (which are already under development for different reasons) could become a major new therapy for Multiple Sclerosis.Read moreRead less
Understanding How Language And Reading Problems Develop: A Population-based Longitudinal Study From Infancy To Age 7
Funder
National Health and Medical Research Council
Funding Amount
$667,507.00
Summary
Early language and reading problems are common and therefore significant public health problems. They are disabling and have life-long implications for oral and written communication skills, social and emotional well-being, cognition, behaviour, academic achievement and employment. This study will address the following three problems: 1. To date no study has documented how language and reading problems develop from infancy (8 months) through to school age (7 years). 2. Little is known about risk ....Early language and reading problems are common and therefore significant public health problems. They are disabling and have life-long implications for oral and written communication skills, social and emotional well-being, cognition, behaviour, academic achievement and employment. This study will address the following three problems: 1. To date no study has documented how language and reading problems develop from infancy (8 months) through to school age (7 years). 2. Little is known about risk factors, identified early in infancy and childhood, that can be reliably used to predict language and reading problems later in childhood. 3. The relationships between language difficulties and reading problems are poorly understood. Therefore, we currently have no satisfactory methods for reliably detecting which children at much younger ages are at risk of later language disorders or reading problems. Without this information it is impossible to develop effective prevention and early intervention programs. These programs are critical if we are to: a) Prevent language and reading problems from occurring, thereby reducing the prevalence of the problem b) Intervene early in childhood, thereby reducing in the longer term the burden and cost associated with language and reading problems. The proposed study builds on an existing substantial investment by the NHMRC in the Early Language in Victoria Study (ELVS). It will provide a world-first description of the evolution of language difficulties and reading problems from infancy through to school age within a single population cohort.Read moreRead less
The Role Of Rnd Genes During Cortical Neurogenesis And Cell Migration
Funder
National Health and Medical Research Council
Funding Amount
$410,384.00
Summary
In order for the brain to function properly, tens of billions of neurons within it first have to be born, then find their proper location before connecting with other neurons in a highly ordered fashion. Failure of these key processes heavily impacts on subsequent brain function, and have been shown to underlie several disorders including epilepsy. This study will investigate how members of the Rnd gene family control cell production and positioning within the developing brain.